Experiments are designed to describe the nature and to define the cause of the brain damage resulting in mental retardation in phenylketonuria. Our hypothesis is that one or more of the metabolites derived from phenylalanine, which are produced in excessive amounts in phenylketonuria may induce retardation of neuronal development. Phenylethylamine and its metabolic products, phenylacetic and mandelic acids, and phenylpyruvic acid and its major end product, phenyllactic acid, will be examined individually for biochemical alterations of the developing brain. These will be related to behavioral changes. Myelination and synaptogenesis will be measured by biochemical procedures. The development of reflexes and of more complex behavior patterns will be studied in pups, and subsequently, tests of activity level, emotionality, sensory, motor and associative function will be given. We will investigate the role of pyridoxamine, a B6 vitamer, in central nervous system function and its efficacy in preventing any aberrations observed in our experiments.